Content uploaded by Eric DB Goulet
Author content
All content in this area was uploaded by Eric DB Goulet on Jan 18, 2015
Content may be subject to copyright.
547
International Journal of Sport Nutrition and Exercise Metabolism, 2009, 19, 547-560
© 2009 Human Kinetics, Inc.
Review of the Effects of Glycerol-
Containing Hyperhydration Solutions
on Gastric Emptying and Intestinal
Absorption in Humans and in Rats
Eric D.B. Goulet
Glycerol-induced hyperhydration (GIH) has been shown to improve uid retention
and endurance performance compared with water-induced hyperhydration. The goal
of this article is to report on what is known and unknown about how glycerol-
containing hyperhydration solutions (GCHSs) are processed at the stomach and intes-
tine level, propose strategies to improve the efcacy of GIH, and provide research
questions for future studies. Through statistical analyses, it is demonstrated that the
effectiveness of GCHSs in increasing uid retention is maximized when uid inges-
tion is in the upper range of what is normally administered by studies (~26 ml/kg
body weight) and the duration of the protocol is no longer than the time it takes for
the glycerol-uid load to be totally or nearly completely integrated inside the body.
The rate of gastric emptying and intestinal absorption of GCHSs is unknown. How-
ever, based on an analysis of indirect evidence obtained from human studies, it is
proposed that most glycerol (~80 g) and uid (~1,700 ml) ingested during a typical
GIH protocol can be integrated inside the body within 60–90 min. Whether the stress
associated with competition could alter these gures is unknown. Research in rats
indicates that combining glycerol with glucose at a 3:1 ratio accelerates intestinal
absorption of both glycerol and water, thereby potentially improving the efcacy of
GIH. Human studies must be conducted to determine how GCHSs are processed by
the gastrointestinal system and whether adding glucose to GCHSs could improve the
technique’s efcacy.
Keywords: overhydration, ergogenic aid, gastrointestinal function, stomach,
intestine
Although change in body weight (BW) is not always a reliable measure of
changes in hydration status (Maughan, Shirreffs, & Leiper, 2007), it is suggested
that an exercise-induced loss in BW of > 2% can impair endurance performance
(American College of Sports Medicine et al., 2007; Cheuvront, Carter, & Sawka,
The author was with the McGill University Health Centre, Royal Victoria Hospital, Montréal, Québec,
Canada, at the time of this study. He is now with the University of Sherbrooke, FEPS, Sherbrooke,
Québec, Canada J1K 2R1.
SCHOLARLY REVIEWS
548 Goulet
2003). Evidence indicates that endurance athletes lose more than 2% BW during
prolonged exercise (Noakes, 1993). The use of preexercise hyperhydration, by
delaying or preventing the 2% BW loss threshold, could therefore be advanta-
geous in situations in which it is anticipated that a BW loss >2% could occur if the
exercise is started in a euhydrated state only.
In a recent meta-analysis (Goulet, Aubertin-Leheudre, Plante, & Dionne,
2007), glycerol-induced hyperhydration (GIH) was demonstrated to signicantly
enhance uid retention and power output during prolonged exercise by 50% and
2.6%, respectively, compared with water-induced hyperhydration. Moreover, it
has recently been shown that, compared with preexercise euhydration, GIH
improved peak power output by 5% during an incremental test to exhaustion after
2 hr of cycling during which uid consumption replaced only 33% of sweat losses
(Goulet, Rousseau, Lamboley, Plante, & Dionne, 2008).
Some individual studies showed no effect of GIH on endurance performance
compared with water-induced hyperhydration (Goulet, Robergs, Labrecque,
Royer, & Dionne, 2006; Marino, Kay, & Cannon, 2003; Nishijima et al., 2007;
Wingo et al., 2004). Moreover, the effects of GIH on cardiovascular and thermo-
regulatory functions during prolonged exercise are equivocal (Nelson & Robergs,
2007). The discrepancy between ndings could result from the different GIH and
exercise protocols used by studies.
Isotonic sodium-containing hyperhydration solutions have been shown to
improve endurance performance compared with hypotonic solutions (Coles &
Luetkemeier, 2005; Sims, Rehrer, Bell, & Cotter, 2007). However, the use of GIH
may prove more advantageous than sodium-induced hyperhydration, because it
has been shown to improve uid retention signicantly more (Grifn et al.,
1999).
Three review articles found in the literature provide important insights into
the physiology of GIH (Latzka & Sawka, 2000; Nelson & Robergs, 2007; Robergs
& Grifn, 1998). Taken together, those articles cover most of the aspects of GIH,
including a review of the biochemistry and pharmacokinetics of glycerol and how
GIH affects thermoregulatory and cardiovascular functions, as well as uid reten-
tion and plasma volume regulation, before, during, and after exercise. However,
no review has been done reporting on how glycerol-containing hyperhydration
solutions (GCHSs) are processed at the stomach and intestine level. This is an
issue that merits particular attention, because the stomach and gut represent the
two barriers that need to be crossed before any of the water and glycerol ingested
during GIH can be integrated into the body uid pools to produce their respective
physiological effects. Therefore, understanding how GCHSs interact with the
stomach and intestine should help optimize the use and, by extension, the efcacy
of GIH. The goal of this article is to report on what is known and unknown about
how the glycerol and water ingested during GIH are handled by the gastrointesti-
nal system, propose strategies and hypotheses with the hope of improving the
efcacy of this hydration strategy, and provide research questions for future
studies.
The rates of gastric emptying and intestinal absorption of the glycerol and
water ingested during GIH will be discussed. It is important to be aware of those
rates, because, as will be demonstrated, the efcacy of GCHSs in increasing uid
retention is maximized when uid ingestion is in the upper range of what is nor-
Glycerol Hyperhydration and GI Functions 549
mally administered in studies and the duration of the protocol is no longer than the
time it takes for the uid-glycerol load to be totally or nearly completely inte-
grated inside the body. Because of the lack of human studies, an attempt will be
made to predict those rates based on an analysis of indirect data obtained from
relevant human studies.
Research in rats that looked at the gastric absorption of glycerol, the intestinal
absorption rate of glycerol, and the intestinal absorption rate of the water ingested
with glycerol will be reviewed. Furthermore, the mechanisms involved in the
absorption of glycerol at the brush border of the intestine and how these facilitate
water absorption will also be discussed.
Glycerol and Glycerol-Induced Hyperhydration
What Is Glycerol?
Glycerol is also known as glycerin, trihydroxypropane, and 1,2,3-propanetriol. It
is a naturally occurring 3-carbon alcohol metabolite (C3H8O3) that constitutes the
structural core of the triglyceride molecules in humans (Frank, Nahata, & Hilty,
1981). Glycerol is an extremely sweet-tasting substance, which is colorless, odor-
less, and viscous. It is a potent osmotic agent, which has a molecular weight of
92.10 and a specic gravity of 1.26. Glycerol is usually available in pharmacies,
and its use is considered safe (Robergs & Grifn, 1998).
Glycerol-Induced Hyperhydration
Volume of Fluid. Studies have administered 20–29 ml of uid/kg BW (1,400–
2,200 ml), with an average corresponding to 24 ml/kg BW, or 1,700 ml (Ander-
son, Cotter, Garnham, Casley, & Febbraio, 2001; Coutts, Reaburn, Mummery, &
Holmes, 2002; Freund et al., 1995; Goulet et al., 2006, 2007, 2008; Grifn et al.,
1999; Hitchins et al., 1999; Latzka et al., 1997, 1998; Lyons, Riedesel, Meuli, &
Chick, 1990; Magal et al., 2003; Marino et al., 2003; Montner et al., 1996, 1999;
Nishijima et al., 2007; O’Brien, Freund, Young, & Sawka, 2005; Riedesel, Allen,
Peake, & Al-Qattan, 1987; Wingo et al., 2004). As shown in Figure 1, there is a
signicant positive correlation between the quantity of uid administered and the
ability of GCHSs to increase uid retention. Hence, the efcacy of GIH is maxi-
mized when the volume of uid administered is in the upper range of the quanti-
ties normally provided. Goulet et al. (2007) indicated that a uid dose of 26 ml/kg
BW should maximize uid retention.
Quantity of Glycerol. Studies have administered 0.9–1.5 g glycerol/kg BW (69–
110 g), with an average corresponding to 1.1 g/kg BW, or 80 g (Anderson et al.,
2001; Coutts et al., 2002; Freund et al., 1995; Goulet et al., 2006, 2007, 2008;
Grifn et al., 1999; Hitchins et al., 1999; Latzka et al., 1997, 1998; Lyons et al.,
1990; Magal et al., 2003; Marino et al., 2003; Montner et al., 1996, 1999;
Nishijima et al., 2007; O’Brien et al., 2005; Riedesel et al., 1987; Wingo et al.,
2004). There is no signicant relationship between the amount of glycerol
administered and the efcacy of GCHSs in increasing uid retention. This might
be because of the lack of variation in the amount of glycerol administered by
550 Goulet
studies. Nevertheless, Goulet et al. (2007) indicated that the ideal quantity of
glycerol ingested to maximize uid retention is 1–1.2 g/kg BW.
Some studies administered the glycerol as a bolus at the start of the ingestion
protocol (Freund et al., 1995; Latzka et al., 1997, 1998; Lyons et al., 1990; Magal
et al., 2003; Montner et al., 1996, 1999; Nishijima et al., 2007; O’Brien et al.,
2005; Riedesel et al., 1987), whereas others mixed it with the total uid load to be
ingested throughout the protocol (Anderson et al., 2001; Coutts et al., 2002;
Goulet et al., 2006, 2008; Grifn et al., 1999; Hitchins et al., 1999; Marino et al.,
2003; Nishijima et al., 2007; Wingo et al., 2004). A statistical analysis (indepen-
dent t test) reveals that the uid retention provided by both types of protocols does
not differ signicantly (Figure 2). Because of glycerol’s sweetness, it must be
noted that ingesting it as a bolus may produce side effects such as nausea and
vomiting (Latzka et al., 1997).
Length of Protocol. Studies that looked at the effect of GIH before exercise
used protocols ranging in length from 60 to 180 min (Anderson et al., 2001;
Coutts et al., 2002; Goulet et al., 2006, 2008; Hitchins et al., 1999; Latzka et al.,
1997, 1998; Lyons et al., 1990; Magal et al., 2003; Marino et al., 2003; Montner
et al., 1996, 1999; Nishijima et al., 2007; Wingo et al., 2004). Four studies with no
exercise period examined the effect of GIH on total body water during time peri-
ods ranging from 210 to 300 min (Freund et al., 1995; Grifn et al., 1999; O’Brien
et al., 2005; Riedesel et al., 1987). The average length of a typical GIH protocol is
136 min (Goulet et al., 2007). There is a trend toward an inverse relationship
between the effectiveness of GCHSs in increasing uid retention and protocol
length (r = –.38, p = .09, n = 22 studies).
Figure 1 — Correlation between relative volume of uid administered during glycerol-
induced hyperhydration and the relative uid retention provided by glycerol-induced hy-
perhydration. N = 22 studies.
Glycerol Hyperhydration and GI Functions 551
Elapsed Time Between End of GCHS Ingestion and Start of Exercise. The
interval of time between the end of ingestion of GCHSs and the start of exercise
may signicantly affect GCHSs’ ability to increase uid retention. It varies a lot
between studies, with values ranging from 0 to 120 min. As shown in Figure 3,
there is a signicant negative relationship between the uid retention provided by
GCHSs and the elapsed time between the end of ingestion of the uid-glycerol
load and the start of exercise. This suggests that the effectiveness of a GIH proto-
col in increasing uid retention should be maximized when its duration equals the
minimum time it takes for the uid-glycerol load to be totally or nearly com-
pletely integrated inside the body. In fact, if the ingestion period and/or waiting
time after ingestion are too long, a substantial part of the circulating uid-glycerol
load will be excreted through the kidneys before exercise. This will reduce uid
retention and diminish the physiological effect of the strategy during exercise.
However, based on results shown in Figure 3, one should note that for any elapsed
time between the end of ingestion of the uid-glycerol load and the start of exer-
cise there could be some variations in uid retention between individuals.
Predictors of GCHSs’ Ability to Increase Fluid Retention. To determine the
best predictors of the efcacy of GCHSs in increasing uid retention, ve key
variables (glycerol and uid dose, length of protocol, whether or not glycerol was
administered as a bolus, and the time span between the end of ingestion and start
of exercise) were entered in a stepwise regression analysis. Only the time span
between the end of ingestion and start of exercise was retained in the model,
explaining 25% of the variation in uid-retention results. Using a hierarchical
regression analysis with all ve variables entered separately, the quantity of uid
administered along with the time span between the end of ingestion and start of
Figure 2 — Difference in uid retention between glycerol-induced-hyperhydration proto-
cols using glycerol boluses or not. Results are M ± SEM. N = 22 studies.
552 Goulet
exercise explained 50% of the variation in uid-retention results, with the other
variables not contributing in signicantly improving the model. Taken together,
the previous ndings emphasize the importance of trying to dene as precisely as
possible the rate of gastric emptying and intestinal absorption of the glycerol and
water ingested during GIH to better dene the optimal length of a GIH protocol.
Handling of Glycerol by the Stomach and Intestine
Gastric-Emptying and Intestinal-Absorption Rates
of Glycerol in Humans
No study has yet evaluated the rates of gastric emptying and intestinal absorption
of glycerol in humans and whether they are dose dependent. Therefore, research
is needed on these topics. Despite the lack of human studies, indirect evidence
indicates that glycerol is rapidly emptied from the stomach, absorbed by the intes-
tine, integrated into the body, and distributed among the body uid pools. For
example, Freund et al. (1995) administered a single bolus of 0.9 g glycerol/kg BW
followed by the ingestion of 22 ml of uid/kg BW within a 30-min period and
then observed the changes in plasma glycerol concentration over the next 150
min. A peak plasma glycerol concentration of 1,250 mg/L was reached 60 min
after glycerol ingestion, followed by a steady and linear decrease over time
because of glycerol turnover and urinary excretion. Using an identical GIH proto-
col, O’Brien et al. (2005) obtained a peak plasma glycerol value comparable to
Figure 3 — Correlation between the elapsed time between end of ingestion of the uid-
glycerol load and the onset of exercise and the relative retention of uid provided by the
glycerol-induced hyperhydration. N = 17 studies.
Glycerol Hyperhydration and GI Functions 553
that observed by Freund et al. 90 min after glycerol ingestion. Hitchins et al.
(1999) had participants ingest 1 g glycerol/kg BW with 22 ml of uid/kg BW
within a 30-min period and observed a peak plasma glycerol concentration of 920
mg/L 60 min after the end of ingestion. Because glycerol elimination through
urine and metabolism is a relatively slow process—for example, 3 hr after inges-
tion Freund et al. estimated that 62% of the ingested glycerol was still inside the
body—the cited results taken together indicate that the bulk of the ingested glyc-
erol can be integrated inside the body 60–90 min after ingestion. This assumption
is reasonable, because if signicant quantities of glycerol would still have been
absorbed by the intestine after 60–90 min, plasma glycerol values should have
remained at a peak much longer or even continued to increase over time, which
was not the case.
Gastric Emptying and Intestinal Absorption of Glycerol
in Rats
Gastric-Absorption and -Emptying Rates. I am aware of no study that deter-
mined in rats the rate at which glycerol is emptied from the stomach. However, it
has been demonstrated that small quantities of glycerol can be absorbed by the
rats’ stomach wall (Embree, Harris, & Herting, 1956). Those authors argued that
the likely mechanism was passive diffusion, although this hypothesis was not
directly tested. Whether glycerol can be absorbed (and at what rate) from the
human stomach is not known and remains to be studied. However, because
the time glycerol spends in the stomach during GIH is likely short (based on the
observations reported herein), very little glycerol is likely to be absorbed.
Rate of Intestinal Absorption. Yuasa et al. (2003) observed that the rate of glyc-
erol absorption in the rat’s small intestine is rapid. In fact, when they introduced
into 5-cm closed loops of rat small intestine in situ 0.5 ml of glycerol solutions
concentrated at 0.002, 1.0, and 40.0 mM, the fraction of the doses absorbed after
30 min reached 92%, 90%, and 73%, respectively.
Allen, Wingertzahn, Teichberg, and Wapnir (1999) perfused (10–12 ml/hr)
20- to 30-cm long segments of rat jejunum with a low-osmolality (228 mOsm/kg
H2O) solution containing 2.6 g NaCl/L and 7 g/L glycerol over a 3-hr period and
observed a rate of glycerol absorption of 104 nmol · min−1 · cm−1. They also
showed that the presence of glucose improves the rate of intestinal glycerol
absorption. In fact, when they perfused a low-osmolality (225 mOsm/kg H2O)
solution containing 2.6 g NaCl/L, 6 g of glycerol/L, and 1.8 g of glucose/L, the
rate of glycerol absorption increased threefold. Other glycerol:glucose ratios were
tested, but none produced absorption rates as high as the one just reported. Thus,
in rats a ratio of 3 g glycerol for 1 g glucose maximizes the entry of glycerol inside
the body.
This nding could have important practical implications for the formulation
of GCHSs. In fact, it suggests that adding some glucose to a uid-glycerol load
might speed up glycerol absorption into the body and, in turn, lead to a more rapid
creation of the optimal osmotic gradient needed at the kidney level to maximize
uid retention (Nelson & Robergs, 2007). Human studies denitely must be con-
ducted on this topic.
554 Goulet
Kato, Hayashi, Inoue, and Yuasa (2004) showed that some glycerol can be
absorbed by the colon, but at a rate that is about 10 times lower than that of the
small intestine. As a result of the signicant absorption of glycerol taking place in
the small intestine and colon, all orally ingested glycerol is made available to the
body (Sommer, Nau, Wieland, & Prange, 1993). The fact that studies on GIH did
not report diarrhea supports this idea.
Mechanisms of Glycerol Absorption. Because glycerol is a small hydrophilic
solute (Kato et al., 2004), it was assumed until recently that its absorption by the
small intestine was occurring strictly by passive diffusion via the paracellular
route (Yuasa et al., 2003). However, using the in vitro everted-sac method involv-
ing the rat small intestine, Kato et al. showed that the transport of glycerol through
the epithelial cells is saturable and primarily mediated by sodium-dependent and
secondary active carriers and, to a lesser extent, by passive diffusion. In the colon,
glycerol uptake is also saturable and also likely governed by a sodium-dependent
carrier-mediated transport system (Kato et al.). It is known that a group of
aquaglyceroporins found in rat and human intestine acts as channels for small
neutral solutes such as urea and glycerol (Kato et al.). However, it was argued by
Kato et al. that it is unlikely these aquaglyceroporins are involved in the carrier-
mediated transport of glycerol, because permeation through channels is expected
to be a linear process (unsaturable), therefore kinetically different from the satu-
rable transport found for glycerol.
Glucose is actively transported along with sodium from the lumen of the
small intestine into the cytoplasm of the enterocytes (Leiper, 1998). The reason
for glucose’s capacity to increase glycerol transport across the mucosa of the
small intestine is likely that its presence allows for the recruitment of more
sodium- dependent active carriers that are also needed for the absorption of glyc-
erol (Allen et al., 1999). Another mechanism may explain the facilitating effect of
glucose on glycerol absorption. Paracellular transport is coupled with sodium-
dependent transcellular transport because the latter mechanism provides the
osmotic force for solvent drag between the enterocytes and increases the perme-
ability of absorptive cells (Leiper; Schedl, Maughan, & Gisol, 1994). Hence, the
presence of glucose may enhance glycerol absorption through increased paracel-
lular transport of glycerol.
Processing of the Water Ingested
Along With Glycerol by the Stomach and Intestine
Gastric-Emptying and Intestinal-Absorption Rates
of the Fluid Ingested During GIH in Humans
No study has yet determined in humans the rate at which the water ingested with
glycerol is emptied from the stomach and absorbed by the gut. It will thus be
important to shed some light on these issues in future studies. There has also been
no study conducted examining the rate at which the uid ingested with glycerol is
emptied from the stomach of rats or any other animals.
Glycerol Hyperhydration and GI Functions 555
Studies that evaluated the effect of carbohydrate-electrolyte solutions on the
rate of gastric emptying and intestinal absorption in humans could provide some
insights into the speed at which GIH could be integrated inside the body. The rst
barrier to the availability of ingested uids is the rate of gastric emptying, which
is a reection of the rate at which uid is delivered to the absorptive surface of the
small intestine (Leiper, 1998). The primary determinants of the rate of gastric
emptying are gastric volume and the energy density of the ingested uid (Noakes,
Rehrer, & Maughan, 1991).
Typical GCHSs composed of 80 g of glycerol and 1,700 ml of uid have an
energy density of 5%. According to Noakes et al. (1991), who estimated the effect
of drinking pattern (volume) and energy density (via carbohydrate) on gastric-
emptying rate, 60 min should be long enough for complete or nearly complete
emptying of the water contained in a typical glycerol solution if an initial intake
of 600 ml is followed by ingestion of 300 ml every 10 min for 40 min. Although
the ingestion of such a uid load in this short amount of time may seem physio-
logically unreasonable, it must be noted that Coutts et al. (2002) and Lyons et al.
(1990) administered uid-glycerol loads of 2 L within 60 min and observed no
side effect other than minor gastrointestinal bloating that disappeared shortly after
the end of ingestion. Hitchins et al. (1999) and Anderson et al. (2001) adminis-
tered a uid-glycerol load of ~1.5 L in 30 min and 15 min, respectively, and
reported no symptoms of discomfort or gastrointestinal distress. On the other
hand, up to, but not more than, 90 min should be required to empty such a uid-
glycerol load if a slightly more “manageable and conservative” drinking pattern
would be employed (initial bolus of 600 ml, followed by 400 ml every 20 min for
60 min). Such a GIH protocol has been shown to be very well tolerated by athletes
and to produce no side effects (Goulet et al., 2008). The absence of side effects in
these protocols suggests that GIH likely produces very high rates of gastric emp-
tying. The decision to use a 60- or 90-min protocol depends on individual toler-
ance of high gastric volume.
It is not easy from human studies to provide an approximation of the rate of
intestinal absorption of typical GCHSs. The principal determinant of the rate of
intestinal water absorption is the osmolality of the ingested solution (Leiper,
1998). Typical GCHSs have an osmolality of ~500 mOsm/kg H2O. Using the
triple- lumen tube technique with humans, Duchman et al. (1997) perfused a
40-cm duodenojejunum test segment with a glucose-electrolyte solution (energy
density of 6% and osmolality of 400 mOsm/kg H2O, both factors comparable to
typical GCHSs) at rates equivalent to the purported rates of gastric emptying of a
typical uid-glycerol load when ingested in the ways reported previously—18 or
28 ml/min—and obtained on average a rate of uid absorption of 13 ml · cm−1 ·
hr−1. Shi et al. (1994) perfused the duodenojejunum (40-cm test segment) of 6
male volunteers with a 6%, 400-mOsm/kg H2O glucose/fructose electrolyte solu-
tion at a rate of 15 ml/min and observed a rate of uid absorption of 16 ml · cm−1
· hr−1. Taken together, these results indicate a possible uid-absorption rate of
GCHSs of ~600 ml/hr, or 900 ml/90 min, over the distal duodenum and proximal
jejunum. The duodenojejunum’s length is ~275 cm, so obviously uid absorption
will occur throughout this segment but at a rate that will be reduced compared
with its proximal section because of the reduction in uid ow rate and total
556 Goulet
solute absorption (Lambert, Chang, Xia, Summers, & Gisol, 1997). After the
rst 75 cm of the duodenojejunum, uid-absorption rates of a carbohydrate-elec-
trolyte solution and a water solution have been shown to be similar because at this
stage both solutions have reached isotonicity and, therefore, the osmotic gradient
for uid absorption is comparable between solutions (Lambert et al.). Santangelo
and Krejs (1985) perfused human stomachs with water (22 ml/min) and examined
water absorption at 140 cm into a jejunum test segment. Their results indicated a
rate of uid absorption on the order of 2 ml · cm−1 · hr−1. Soergel, Whalen, and
Harris (1968) perfused human ileums (30-cm test segment) with an isotonic solu-
tion at a rate of 9–9.5 ml/min and observed a rate of uid absorption of 1 ml · cm−1
· hr−1. Given the length of the duodenojejunum and ileum (300 cm), and if it is
assumed that uid absorption from the rst 50 cm of the duodenojejunum is 600
ml/hr, for the remainder of the duodenojejunum is 500 ml/hr, and for the ileum is
300 ml/hr, then the maximal absorptive capacity of the small intestine for GCHSs
could be ~1,400 ml/hr.
The change in plasma volume reects the net effect of uid absorption (Shi
et al., 1994). Gisol, Summers, Lambert, and Xia (1998) showed that a hypertonic
carbohydrate-electrolyte solution is absorbed as rapidly as water in the distal duo-
denum and proximal jejunum and that both solutions have a similar effect on
plasma volume regulation during exercise. Over a 3-hr period, Freund et al. (1995)
demonstrated that GCHSs do not alter plasma volume compared with water, in-
directly suggesting that they are absorbed as fast as water or a carbohydrate-
electrolyte solution.
Although the composition of GCHSs differs from that of a carbohydrate-
electrolyte solution, based on the results reported here, it is reasonable to suggest
that the water found in standard GCHSs is likely to be totally or nearly totally
integrated inside the body within a period of 60 min if an aggressive drinking pat-
tern is used and within 90 min when a more “relaxed” drinking pattern is used.
This assumption obviously needs to be tested in futures studies.
It is important to note that the effect of GIH on endurance performance has
been tested only under controlled laboratory conditions and not in real-world
stressful situations such as before key competitions. This is an important factor
that ultimately prevents us from knowing or advocating an optimal timing of
ingestion before competition. For example, nervousness before competition might
alter gastrointestinal kinetics. On the other hand, nobody has demonstrated that
uid retention and the ergogenic benet of GCHSs could not be maximized for
some competitions (e.g., cycle road race or ultradistance triathlon) when drinking
is accelerated or completed at exercise onset. This would allow uid-conservation
responses to be initiated before the volume load takes full effect and thus might
attenuate diuresis. Research is needed to delineate the effect of stress on gastroin-
testinal symptoms during GIH.
Intestinal Absorption of Water Ingested With Glycerol in Rats
Rate of Absorption. Previously, using procedures that have been reported here,
Allen et al. (1999) determined the rate of intestinal absorption of water ingested
with glycerol in rat jejunum. In this segment of the intestine, they observed a
mean rate of water absorption of 0.96 µl · min−1 · cm−1 when a low-osmolality
Glycerol Hyperhydration and GI Functions 557
(228 mOsm/kg H2O) solution composed of 2.6 g NaCl/L and 7 g/L glycerol was
perfused over a 3-hr period. On the other hand, the perfusion of a glucose solution
(2.6 g NaCl/L with 13.5 g glucose/L, 243 mOsm/kg H2O) allowed a rate of water
absorption of 1.6 µl · min−1 · cm−1. However, when solutions (all containing 2.6 g
NaCl/L) with the same osmolar load but composed of glycerol and glucose at a
ratio of 25:50, 37.5:37.5, 50:25, and 65:10 (mmol/L) were perfused, the rate of
water absorption increased to 1.9, 2.1, 2.8,and 2.6 µl · min−1 · cm−1, respectively.
These latter rates of intestinal absorption are interesting in that they were signi-
cantly greater than those allowed by the perfusion of either the glycerol or glucose
solution alone. Wapnir, Sia, and Fisher (1996) arrived at similar conclusions and
showed that the presence of glycerol in a rehydration formula comprising carbo-
hydrate, sodium citrate, and potassium enhances the rate of water absorption into
the body compared with a rehydration formula devoid of glycerol.
Taken together, the foregoing results suggest that adding glucose to GCHSs
could increase the rate of water absorption and, thus, potentially accelerate the
hyperhydration process. On the other hand, adding glucose to GCHSs will further
increase their energy density, which may slow gastric emptying and nullify the
facilitating effect of glucose on uid absorption. Studies must be conducted to
determine how the combination of glucose and glycerol inuences uid absorp-
tion in humans.
Mechanism of Glycerol-Induced Water Absorption. Water movement into the
absorptive cells is a passive process. The transport of solutes moves water into the
enterocytes down the osmotic gradient produced by solute movements. As reported
here, the absorption of glycerol is mediated via sodium-dependent and secondary
active transport and, to a lesser extent, by passive diffusion. As glycerol is trans-
ported along with sodium, the excess water ingested during hyperhydration will
follow those two solutes as the transport process creates a favorable osmotic gra-
dient. Obviously, the fact that glycerol is a small molecule with hydrophilic prop-
erty offers a clear advantage for water transport across the mucosal brush borders
(Wapnir et al., 1996).
The combination of glucose and glycerol has been shown to improve uid
absorption in rats. The concomitant ingestion of glucose and glycerol likely poten-
tiates water absorption by activating more and diverse active sodium-nutrient
cotransporters, as well as allowing a greater efux of water between enterocytes.
Conclusions
There are currently no studies that have been conducted that determined in humans
the rate of gastric emptying and intestinal absorption of GCHSs. It is important to
pursue studies on these issues in the future. It was demonstrated in this review that
the best predictor of the efcacy of GCHSs in increasing uid retention was the
elapsed time between the end of ingestion of a GCHS and the onset of exercise:
The shorter it is, the higher will be the retention of uid. This suggests that the
efcacy of GIH is maximized when the duration of the protocol is no longer than
the time it takes for the uid-glycerol load to be totally or nearly completely inte-
grated inside the body. The amount of uid ingested during GIH also has an
important impact on the efcacy of GIH: The higher the amount of uid ingested,
558 Goulet
the higher the retention of uid. However, this factor has less impact on the ef-
cacy of GIH than the elapsed time between the end of ingestion of the uid-
glycerol load and the onset of exercise, at least with the uid doses that have been
administered in studies. These ndings combined together emphasize the impor-
tance of being aware of the rate of gastric emptying and intestinal absorption of
GCHSs. Based on indirect evidence provided by human studies, it is proposed
that a GIH protocol lasting 60–90 min should be sufcient for the integration of
all or nearly all water and glycerol inside the body. Whether this assumption
makes sense needs to be tested in future studies. Research in rats suggests that
combining glycerol with glucose at a 3:1 ratio can accelerate the rate of glycerol
and uid absorption in the intestine, thereby potentially speeding up the hyperhy-
dration process and further improving the efcacy of GIH. Whether similar results
could be obtained in humans must be tested. The stress associated with competi-
tion may slow gastrointestinal function. Whether this could prolong the time
required for the uid-glycerol load to be integrated inside the body requires fur-
ther investigation.
Acknowledgments
The author is supported by the Fonds de la recherche en santé du Québec (FRSQ) and
reports no conict of interest with any organizations.
References
Allen, L.A., Wingertzahn, M.A., Teichberg, S., & Wapnir, R.A. (1999). Proabsorptive
effect of glycerol as a glucose substitute in oral rehydration solutions. The Journal of
Nutritional Biochemistry, 10, 49–55.
American College of Sports Medicine, Sawka, M.N., Burke, L.M., Randy Eichner, E.,
Maughan, R.J., Montain, S.J., & Stachenfeld, N.S. (2007). American College of
Sports Medicine position stand. Exercise and uid replacement. Medicine and Sci-
ence in Sports and Exercise, 39, 377–390.
Anderson, M.J., Cotter, J.D., Garnham, A.P., Casley, D.J., & Febbraio, M.A. (2001). Effect
of glycerol-induced hyperhydration on thermoregulation and metabolism during exer-
cise in heat. International Journal of Sport Nutrition and Exercise Metabolism, 11,
315–333.
Cheuvront, S.N., Carter, R., 3rd, & Sawka, M.N. (2003). Fluid balance and endurance
exercise performance. Current Sports Medicine Reports, 2, 202–208.
Coles, M.G., & Luetkemeier, M.J. (2005). Sodium-facilitated hypervolemia, endurance
performance, and thermoregulation. International Journal of Sports Medicine, 26,
182–187.
Coutts, A., Reaburn, P., Mummery, K., & Holmes, M. (2002). The effect of glycerol hy-
perhydration on Olympic distance triathlon performance in high ambient tempera-
tures. International Journal of Sport Nutrition and Exercise Metabolism, 12, 105–119.
Duchman, S.M., Ryan, A.J., Schedl, H.P., Summers, R.W., Bleiler, T.L., & Gisol, C.V.
(1997). Upper limit for intestinal absorption of a dilute glucose solution in men at rest.
Medicine and Science in Sports and Exercise, 29, 482–488.
Embree, N.D., Harris, P.L., & Herting, D.C. (1956). Absorption of acetic acid and glycerol
from the rat stomach. The American Journal of Physiology, 187, 224–226.
Frank, M.S., Nahata, M.C., & Hilty, M.D. (1981). Glycerol: A review of its pharmacology,
pharmacokinetics, adverse reactions, and clinical use. Pharmacotherapy, 1, 147–160.
Glycerol Hyperhydration and GI Functions 559
Freund, B.J., Montain, S.J., Young, A.J., Sawka, M.N., DeLuca, J.P., Pandolf, K.B., et
al. (1995). Glycerol hyperhydration: Hormonal, renal, and vascular uid responses.
Journal of Applied Physiology, 79, 2069–2077.
Gisol, C.V., Summers, R.W., Lambert, G.P., & Xia, T. (1998). Effect of beverage osmolal-
ity on intestinal uid absorption during exercise. Journal of Applied Physiology, 85,
941–948.
Goulet, E.D., Robergs, R.A., Labrecque, S., Royer, D., & Dionne, I.J. (2006). Effect of
glycerol-induced hyperhydration on thermoregulatory and cardiovascular functions
and endurance performance during prolonged cycling in a 25°C environment. Applied
Physiology, Nutrition, and Metabolism, 31, 101–109.
Goulet, E.D.B., Aubertin-Leheudre, M., Plante, G.E., & Dionne, I.J. (2007). A meta-analy-
sis of the effects of glycerol-induced hyperhydration on uid retention and endurance
performance. International Journal of Sport Nutrition and Exercise Metabolism, 17,
391–410.
Goulet, E.D.B., Rousseau, S.F., Lamboley, C.R.H., Plante, G.E., & Dionne, I.J. (2008).
Pre-exercise hyperhydration delays dehydration and improves endurance capacity
during 2 h of cycling in a temperate climate. Journal of Physiological Anthropology,
27, 263–271.
Grifn, S.E., Ghiasvand, F., Gibson, A., Orri, J., Burns, S., & Robergs, R.A. (1999). Com-
paring hyperhydration resulting from the ingestion of glycerol, carbohydrate and
saline solutions [abstract]. Journal of Exercise Physiology, 2, abstract 2. Retrieved
from http://faculty.css.edu/tboone2/asep/sharon.pdf
Hitchins, S., Martin, D.T., Burke, L., Yates, K., Fallon, K., Hahn, A., et al. (1999). Glycerol
hyperhydration improves cycle time trial performance in hot humid conditions. Euro-
pean Journal of Applied Physiology, 80, 494–501.
Kato, T., Hayashi, Y., Inoue, K., & Yuasa, H. (2004). Functional characterization of the
carrier-mediated transport system for glycerol in everted sacs of the rat small intes-
tine. Biological & Pharmaceutical Bulletin, 27, 1826–1830.
Lambert, G.P., Chang, R.T., Xia, T., Summers, R.W., & Gisol, C.V. (1997). Absorption
from different intestinal segments during exercise. Journal of Applied Physiology, 83,
204–212.
Latzka, W.A., & Sawka, M.N. (2000). Hyperhydration and glycerol: Thermoregulatory
effects during exercise in hot climates. Canadian Journal of Applied Physiology, 25,
536–545.
Latzka, W.A., Sawka, M.N., Montain, S.J., Skrinar, G.S., Fielding, R.A., Matott, R.P., et al.
(1997). Hyperhydration: Thermoregulatory effects during compensable exercise-heat
stress. Journal of Applied Physiology, 83, 860–866.
Latzka, W.A., Sawka, M.N., Montain, S.J., Skrinar, G.S., Fielding, R.A., Matott, R.P., et al.
(1998). Hyperhydration: Tolerance and cardiovascular effects during uncompensable
exercise-heat stress. Journal of Applied Physiology, 84, 1858–1864.
Leiper, J.B. (1998). Intestinal water absorption—Implications for the formulation of rehy-
dration solutions. International Journal of Sports Medicine, 19(Suppl. 2), S129–
S132.
Lyons, T.P., Riedesel, M.L., Meuli, L.E., & Chick, T.W. (1990). Effects of glycerol-induced
hyperhydration prior to exercise in the heat on sweating and core temperature. Medi-
cine and Science in Sports and Exercise, 22, 477–483.
Magal, M., Webster, M.J., Sistrunk, L.E., Whitehead, M.T., Evans, R.K., & Boyd, J.C.
(2003). Comparison of glycerol and water hydration regimens on tennis-related per-
formance. Medicine and Science in Sports and Exercise, 35, 150–156.
Marino, F.E., Kay, D., & Cannon, J. (2003). Glycerol hyperhydration fails to improve
endurance performance and thermoregulation in humans in a warm humid environ-
ment. Pugers Archiv, 446, 455–462.
560 Goulet
Maughan, R.J., Shirreffs, S.M., & Leiper, J.B. (2007). Errors in the estimation of hydration
status from changes in body mass. Journal of Sports Sciences, 25, 797–804.
Montner, P., Stark, D.M., Riedesel, M.L., Murata, G., Robergs, R., Timms, M., et al. (1996).
Pre-exercise glycerol hydration improves cycling endurance time. International Jour-
nal of Sports Medicine, 17, 27–33.
Montner, P., Zou, Y., Robergs, R.A., Murata, G., Stark, D., Quinn, C., et al. (1999). Glyc-
erol hyperhydration alters cardiovascular and renal function. Journal of Exercise
Physiology online, 2, 1-10.
Nelson, J.L., & Robergs, R.A. (2007). Exploring the potential ergogenic effects of glycerol
hyperhydration. Sports Medicine (Auckland, N.Z.), 37, 981–1000.
Nishijima, T., Tashiro, H., Kato, M., Saito, T., Omori, T., Chang, H., et al. (2007). Allevia-
tion of exercise-induced dehydration under hot conditions by glycerol hyperhydra-
tion. International Journal of Sport and Health Science, 5, 32–41.
Noakes, T.D. (1993). Fluid replacement during exercise. Exercise and Sport Sciences
Reviews, 21, 297–330.
Noakes, T.D., Rehrer, N.J., & Maughan, R.J. (1991). The importance of volume in regulat-
ing gastric emptying. Medicine and Science in Sports and Exercise, 23, 307–313.
O’Brien, C., Freund, B.J., Young, A.J., & Sawka, M.N. (2005). Glycerol hyperhydration:
physiological responses during cold-air exposure. Journal of Applied Physiology, 99,
515–521.
Riedesel, M.L., Allen, D.Y., Peake, G.T., & Al-Qattan, K. (1987). Hyperhydration with
glycerol solutions. Journal of Applied Physiology, 63, 2262–2268.
Robergs, R.A., & Grifn, S.E. (1998). Glycerol. Biochemistry, pharmacokinetics and clini-
cal and practical applications. Sports Medicine (Auckland, N.Z.), 26, 145–167.
Santangelo, W.C., & Krejs, G.J. (1985). Absorption of pure water by the human gastroin-
testinal tract [abstract]. Gastroenterology, 88, 1569.
Schedl, H.P., Maughan, R.J., & Gisol, C.V. (1994). Intestinal absorption during rest and
exercise: Implications for formulating an oral rehydration solution (ORS). Medicine
and Science in Sports and Exercise, 26, 267–280.
Shi, X., Summers, R.W., Schedl, H.P., Chang, R.T., Lambert, G.P., & Gisol, C.V. (1994).
Effects of solution osmolality on absorption of select uid replacement solutions in
human duodenojejunum. Journal of Applied Physiology, 77, 1178–1184.
Sims, S.T., Rehrer, N.J., Bell, M.L., & Cotter, J.D. (2007). Preexercise sodium loading
aids uid balance and endurance for women exercising in the heat. Journal of Applied
Physiology, 103, 534–541.
Soergel, K.H., Whalen, G.E., & Harris, J.A. (1968). Passive movement of water and sodium
across the human small intestinal mucosa. Journal of Applied Physiology, 24, 40–48.
Sommer, S., Nau, R., Wieland, E., & Prange, H.W. (1993). Pharmacokinetics of glycerol
administered orally in healthy volunteers. Arzneimittel-Forschung, 43, 744–747.
Wapnir, R.A., Sia, M.C., & Fisher, S.E. (1996). Enhancement of intestinal water absorp-
tion and sodium transport by glycerol in rats. Journal of Applied Physiology, 81,
2523–2527.
Wingo, J.E., Casa, D.J., Berger, E.M., Dellis, W.O., Knight, J.C., & McClung, J.M. (2004).
Inuence of a pre-exercise glycerol hydration beverage on performance and physi-
ologic function during mountain-bike races in the heat. Journal of Athletic Training,
39, 169–175.
Yuasa, H., Hamamoto, K., Dogu, S.Y., Marutani, T., Nakajima, A., Kato, T., et al. (2003).
Saturable absorption of glycerol in the rat intestine. Biological & Pharmaceutical
Bulletin, 26, 1633–1636.
